Interleukin-1 family consists of interleukin-1 alpha, beta, delta, epsilon, zeta, eta, theta, which are also named IL-1F1, IL1F2, IL1F3, IL1F4, IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, and interleukin-18. These are naturally occurring polypeptides with sequences well-known from the art. The first member of this family, interleukin-1 alpha is synthesized as 31-kDa precursor, and is secreted by cells in active form of about 18-kDa. Interleukin-1 alpha is the only interleukin-1 family member that is constitutively produced in active form by cells of mammalian epidermis including human epidermis. Healthy human skin contains interleukin-1 alpha in levels of about 10 to 20 ng/cm2, which levels are frequently decreased, for example, in conditions of psoriatic or aging skin. Mizutani H, et al., J Clin Invest. 1991, 87(3):1066-71. Wood L C, et al., J Clin Invest 1992: 90: 482-487. Se Kyoo Jeonq, et al., Exp. Dermatology 2005: 14: 571-579. Chantel O., et al., J Invest Dermatol 122:330-336, 2004. Nowinski D, et al, J Invest Dermatol. 2002; 119(2):449-55. Bonifati C, et al., J Biol Requl Homeost Agents. 1997, 11(4):133-6. Takematsu H, et al. Tohoku J Exp Med. 1990, 161(3):159-69.
The use of interleukin-1 family members in medicinal applications is known from the art. For example, U.S. Pat. No. 4,816,436 discloses a process for treating arthritis or inflammation with the use of intra-articular, intramuscular, intravenous, or intraperitoneal injections of interleukin-1 alpha; U.S. Pat. No. 5,120,534 discloses a method for treating thrombocytopenia by administering interleukin-1 alpha or Asp36, Ser141-derivative of interleukin-1 alpha; U.S. Pat. No. 5,534,251 discloses stabilized medicinal composition comprising Asp36, Ser141-derivative of interleukin-1 alpha; EP0391444 discloses a pharmaceutical composition comprising interleukin-1 alpha, and suitable for forming a parenterally administratable aqueous formulation; WO9116916, JP4018033, EP0482213, and ES2121782T disclose an antitumor composition containing the combination of interleukin-1 and gamma-interferon.
However, no published or disclosed in the art related to cosmetic, cosmeceutical, or dermatological compositions comprising interleukin-1 family member and a peptide of the general formula Tyr-X1-X2-Phe-X3-X4-Y, wherein X1, X2, X3, X4 are independently amino acids, and Y is absent or a sequence of 1 to 5 amino acid residues.
The use of interleukin-1 family members in medicinal or cosmetic applications may be limited by side effects linked to pro-inflammatory action of these polypeptides. Thus, there is a great need in agents, which may diminish side effects of interleukin-1 family members.
We found that the use of peptide of general formula Tyr-X1-X2-Phe-X3-X4-Y, wherein X1, X2, X3, X4 are independently amino acids, and Y is absent or a sequence of 1 to 5 amino acid residues, remarkably eliminates undesirable effects of polypeptides of interleukin-1 family members, when said peptides are used in combination with said polypeptides.
It is an object of the present invention to provide pharmaceutical, cosmetic, cosmeceutical, and dermatological compositions comprising interleukin-1 family members and peptide of general formula Tyr-X1-X2-Phe-X3-X4-Y.